a murine alpha-2 macroglobulin (AMG) has been purified from both tumor ascites and normal plasma. AMG, like human alpha-2 macroglobulin (alpha2M), is a protease inhibitor, but these proteins do not share antigenic properties. AMG suppresses the growth of all types of mouse tumor cells investigated, and this suppressive effect is dose dependent. When compared with other protease inhibitors in terms of molar quantities, AMG is by far the most effective in suppressing the growth of mouse ovarian tumor cells in Vitro. AMG also effectively inhibits other rapidly growing cells, such as lymphocytes undergoing blastogenesis induced by both T-cell and B-cell mitogens and allogeneic cells. Current investigations center on elucidating the mechanism of inhibitory action of AMG on neoplastic cells and lymphocytes. Concurrently, we are also studying another immunoregulatory "macroglobulin" associated with a spontaneously regressing tumor subline of L1210 leukemia. This immunoregulatory factor(IRF) can greatly suppress both the primary (IgM and IgG) humoral anti-SRBC and cellular (killer T-cell) immune responses of mice, but it has little or no effect on the T-cells mediating delayed hypersensitivity reactions. IRF does not significantly affect the responsiveness of memory cells, but mice pre-treated with IRF in the cell-free ascitic fluid show greatly enhanced IgM and IgG responses after secondary immunization with SRBC. It appears that IRF asserts its suppressive effects indirectly on the immune cells at the time of sensitization and not at the effector level, and these effects last for at least two weeks in vivo. Current investigation attempts to purify this IRF, to study mechanism of its suppressive activities, and to identify specific immune effector functions important for the spontaneous regression of tumors.